Micro-mold design controls the 3D morphological evolution of self-assembling multicellular microtissues.

Micro-mold design controls the 3D morphological evolution of self-assembling multicellular microtissues.
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微模具设计控制自组装多细胞微组织的 3D 形态演化。

DOI:
10.1089/ten.tea.2013.0297
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发表时间:
2014
影响因子:
--
通讯作者:
Morgan,JeffreyR
Morgan,JeffreyR
中科院分区:
--
文献类型:
--
作者:
Svoronos,AlexanderA;Tejavibulya,Nalin;Schell,JacquelynY;Shenoy,VivekB;Morgan,JeffreyR

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当接种到非粘附性微模具中时,细胞通过细胞间隙介导的收缩和细胞-细胞粘附的作用自组装成三维(3D)多细胞微组织。组织的大小和形状是细胞类型和微模具的大小、形状和障碍物的函数。在这篇文章中,我们使用人类成纤维细胞来研究模具设计的一些元素,以及它们如何用于指导3D组织自组织时发生的形态变化。在具有两个非粘性柱的环端狗骨模具中,成纤维细胞形成自约束组织,其张力诱导形态变化,最终导致组织变薄和破裂。增加狗骨式连接杆的宽度增加稳定性,而增加其长度降低稳定性。绘制破裂点表明,狗骨组织的环形和连接杆区域之间的细胞体积平衡控制了破裂点。当细胞用转化生长因子-β1处理时,由于细胞收缩增加,狗骨状破裂更快。在模具设计中,以形成具有更复杂形状的组织,例如三个互连的环形或蜂窝,障碍物设计控制张力和组织形态。当垂直的柱子变成圆锥体时,它们就变成了张力调节器,决定了在一个大的自组织中何时何地释放张力。通过了解模具设计的元素如何控制形态,我们可以制作更好的模型来研究器官发生,检查3D细胞力学,并为组织工程制造建筑部件。
When seeded into nonadhesive micro-molds, cells self-assemble three-dimensional (3D) multicellular microtissues via the action of cytoskeletal-mediated contraction and cell–cell adhesion. The size and shape of the tissue is a function of the cell type and the size, shape, and obstacles of the micro-mold. In this article, we used human fibroblasts to investigate some of the elements of mold design and how they can be used to guide the morphological changes that occur as a 3D tissue self-organizes. In a loop-ended dogbone mold with two nonadhesive posts, fibroblasts formed a self-constrained tissue whose tension induced morphological changes that ultimately caused the tissue to thin and rupture. Increasing the width of the dogbone's connecting rod increased the stability, whereas increasing its length decreased the stability. Mapping the rupture points showed that the balance of cell volume between the toroid and connecting rod regions of the dogbone tissue controlled the point of rupture. When cells were treated with transforming growth factor-β1, dogbones ruptured sooner due to increased cell contraction. In mold designs to form tissues with more complex shapes such as three interconnected toroids or a honeycomb, obstacle design controlled tension and tissue morphology. When the vertical posts were changed to cones, they became tension modulators that dictated when and where tension was released in a large self-organizing tissue. By understanding how elements of mold design control morphology, we can produce better models to study organogenesis, examine 3D cell mechanics, and fabricate building parts for tissue engineering.
DOI: 10.1089/ten.2005.11.1254
发表时间: 2005-07-01
期刊: TISSUE ENGINEERING
影响因子: --
作者:
Fukuda, J;Nakazawa, K
通讯作者: Nakazawa, K
DOI: 10.1290/1071-2690(2001)037
发表时间: 2001-03-01
影响因子: 2.1
作者:
Liu, XD;Umino, T;Rennard, SI
通讯作者: Rennard, SI